Department of Neurosurgery

CSF Disorders Laboratory

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CSF Disorders Laboratory

Overview

Our research aims to understand the structural and dynamic principles underlying congenital and acquired disorders that disrupt cerebrospinal fluid (CSF) spaces, flow, circulation, and composition. We also focus on the relation of CSF and spine disorders related to Ehlers-Danlos-syndromes, a disorder of connective tissue associated with hypermobility of the spine. Selected Heritable Disorders of Connective Tissue and Disability | National Academies. These CSF-related conditions include Chiari malformation, syringomyelia, tethered cord syndrome, and normal pressure hydrocephalus (NPH).

We are developing a unifying concept of spinal cord motion disorders, exploring how abnormal anchoring of the spinal cord and cerebellum to the rigid spine and skull may connect Chiari malformation and tethered cord. Our group has previously demonstrated the biomechanical roles of the myodural bridges and filum terminale, and we are now investigating how these structures influence craniospinal compliance, skull base dynamics, and segmental spinal motion control.
This work is conducted in close collaboration with Francis Loth, Ph.D., Northeastern University College of Engineering. Francis Loth - Northeastern University College of Engineering and our Center for Innovative Neurotechnology for Neural Repair (CINNR) in Rhode Island.

A second major focus of our research examines the impact of CSF disorders on cognition.
In Chiari malformation, we have identified cerebellar structural changes linked to cognitive decline in both children and adults and demonstrated how cerebellar cognitive measures provide deeper insight into symptom mechanisms and postoperative outcomes. This work is carried out in collaboration with Philip A. Allen, Ph.D., Department of Psychology, University of Akron, Ohio. Philip A. Allen, Ph.D. : The University of Akron, Ohio.

In NPH, our research connects CSF biomarker profiles to cognitive outcomes and dementia risk, in partnership with the Carney Institute for Brain Science at Brown University, as part of the New Biomarkers for Neurodegenerative Disease initiative.

Together, these efforts aim to advance a comprehensive understanding of CSF physiology and pathophysiology, bridging biomechanics, neurobiology, and cognition toward improved diagnosis and treatment of CSF-related diseases. New biomarkers for neurodegenerative disease | Carney Institute for Brain Science | Brown University.

Our Team

  • Petra Klinge, MD

    Petra Klinge, MD, PhD

    Professor of Neurosurgery, Director, Pediatric Neurosurgery, Division Director, Center for Surgical Treatment of the Developing Brain and Spine
  • Patricia Leigh Zadnik Sullivan, MD

    Patricia Leigh Zadnik Sullivan, MD

    Assistant Professor of Neurosurgery, Director, Center for Spine Tumor & Chordoma Research, Member, Legoretta Cancer Center
  • Konstantina Svokos, DO, MS

    Konstantina A. Svokos, DO, MS

    Associate Professor of Neurosurgery and Pediatrics, Director of Fetal Neurosurgery, Co-Director, Neuroplastics, Co-Director, Center for Surgical Treatment of the Developing Brain and Spine, Pediatric Neurosurgeon
  • Maria Guglielmo, MD

    Maria Guglielmo, MD

    Assistant Professor of Neurosurgery, Newport Hospital

Educational Lectures

Think Tank Meeting of the Bobby Jones Foundation - April 25, 2025

Paths Forward: Exploring Future Methods in the Study of and Clinical Practice in Chiari, Syringomyelia, and Related Disorders 

Chiari Malformation: Updates and perspectives on cerebellar cognitive affective syndrome (CCAS) & ultrasound imaging of the myodural bridges - Natalie Amaral-Nieves, MD | Brown University, Providence, RI

Recent/Related Publications

1. PMID: 38755194
Paediatric hydrocephalus.
Kahle KT, Klinge PM, Koschnitzky JE, Kulkarni AV, MacAulay N, Robinson S, Schiff SJ, Strahle JM. Nat Rev Dis Primers. 2024 May 16;10(1):35. doi: 10.1038/s41572-024-00519-9.PMID: 38755194 Free PMC article. Review.

2. PMID: 38489815
Clinical criteria for filum terminale resection in occult tethered cord syndrome.
Klinge PM, Leary OP, Allen PA, Svokos K, Sullivan P, Brinker T, Gokaslan ZL. J Neurosurg Spine. 2024 Mar 15;40(6):758-766. doi: 10.3171/2024.1.SPINE231191. Print 2024 Jun 1. PMID: 38489815

3. PMID: 35902471
Influence of Pain on Cognitive Dysfunction and Emotion Dysregulation in Chiari Malformation Type I.
Houston JR, Maleki J, Loth F, Klinge PM, Allen PA.Adv Exp Med Biol. 2022;1378:155-178. doi: 10.1007/978-3-030-99550-8_11.PMID: 35902471 Free PMC article. Review.

4. PMID: 36515069
Longitudinal post-shunt outcomes in idiopathic normal pressure hydrocephalus with and without comorbid Alzheimer's disease.
Gold D, Wisialowski C, Piryatinsky I, Malloy P, Correia S, Salloway S, Klinge P, Gaudet CE, Niermeyer M, Lee A.J Int Neuropsychol Soc. 2023 Oct;29(8):751-762. doi: 10.1017/S1355617722000868. Epub 2022 Dec 14. PMID: 36515069

5. PMID: 36857788
Reappraisal of intradural findings in Chiari malformation type I.
Shao B, Wojcik D, Ma KL, Amaral-Nieves N, Poggi JA, Leary OP, Klinge PM. Neurosurg Focus. 2023 Mar;54(3):E2. doi: 10.3171/2022.12.FOCUS22628.PMID: 36857788

6. PMID: 36991111
Charlson comorbidity index applied to shunted idiopathic normal pressure hydrocephalus.
Klinge PM, Ma KL, Leary OP, Sastry RA, Sayied S, Venegas O, Brinker T, Gokaslan ZL. Sci Rep. 2023 Mar 29;13(1):5111. doi: 10.1038/s41598-023-32088-4.PMID: 36991111 Free PMC article.

7. PMID: 37208310
Cerebrospinal fluid transcripts may predict shunt surgery responses in normal pressure hydrocephalus.
Levin Z, Leary OP, Mora V, Kant S, Brown S, Svokos K, Akbar U, Serre T, Klinge P, Fleischmann A, Ruocco MG. Brain. 2023 Sep 1;146(9):3747-3759. doi: 10.1093/brain/awad109. PMID: 37208310

8. PMID: 36556053
Compromised Cranio-Spinal Suspension in Chiari Malformation Type 1: A Potential Role as Secondary Pathophysiology.
Shao B, Poggi JA, Amaral-Nieves N, Wojcik D, Ma KL, Leary OP, Klinge PM.J Clin Med. 2022 Dec 15;11(24):7437. doi: 10.3390/jcm11247437.PMID: 36556053 Free PMC article.

9. PMID: 34992329
A new hypothesis for the pathophysiology of symptomatic adult Chiari malformation Type I.
Labuda R, Nwotchouang BST, Ibrahimy A, Allen PA, Oshinski JN, Klinge P, Loth F. Med Hypotheses. 2022 Jan;158:110740. doi: 10.1016/j.mehy.2021.110740. Epub 2021 Dec 14.PMID: 34992329 Free PMC article.

10. PMID: 34106419
Adult Age Differences in Self-Reported Pain and Anterior CSF Space in Chiari Malformation.
García M, Eppelheimer MS, Houston JR, Houston ML, Nwotchouang BST, Kaut KP, Labuda R, Bapuraj JR, Maleki J, Klinge PM, Vorster S, Luciano MG, Loth F, Allen PA. Cerebellum. 2022 Apr;21(2):194-207. doi: 10.1007/s12311-021-01289-w. Epub 2021 Jun 9.PMID: 34106419 Free PMC article.

11. PMID: 31292490
Evaluation of the Structure of Myodural Bridges in an Equine Model of Ehlers-Danlos Syndromes.
McElroy A, Rashmir A, Manfredi J, Sledge D, Carr E, Stopa E, Klinge P.Sci Rep. 2019 Jul 10;9(1):9978. doi: 10.1038/s41598-019-46444-w.PMID: 31292490 Free PMC article.

12. PMID: 38202013
The Surgical Histopathology of the Filum Terminale: Findings from a Large Series of Patients with Tethered Cord Syndrome.
Abdulrazeq H, Leary OP, Tang OY, Karimi H, McElroy A, Gokaslan Z, Punsoni M, Donahue JE, Klinge PM. J Clin Med. 2023 Dec 19;13(1):6. doi: 10.3390/jcm13010006.PMID: 38202013 Free PMC article.

13. PMID: 34020423
Abnormal spinal cord motion at the craniocervical junction in hypermobile Ehlers-Danlos patients.
Klinge PM, McElroy A, Donahue JE, Brinker T, Gokaslan ZL, Beland MD.J Neurosurg Spine. 2021 May 21;35(1):18-24. doi: 10.3171/2020.10.SPINE201765. Print 2021 Jul 1.PMID: 34020423

14. PMID: 37935987
Relationship of Morphometrics and Symptom Severity in Female Type I Chiari Malformation Patients with Biological Resilience.
Al Samman MM, Garcia MA, García M, Houston JR, Loth D, Labuda R, Vorster S, Klinge PM, Loth F, Delahanty DL, Allen PA. Cerebellum. 2024 Jun;23(3):1146-1156. doi: 10.1007/s12311-023-01627-0. Epub 2023 Nov 7.PMID: 37935987 Free PMC article.

15. PMID: 34278303
Functional connectivity abnormalities in Type I Chiari: associations with cognition and pain.
Houston ML, Houston JR, Sakaie K, Klinge PM, Vorster S, Luciano M, Loth F, Allen PA. Brain Commun. 2021 Jun 14;3(3):fcab137. doi: 10.1093/braincomms/fcab137. eCollection 2021 Jul.PMID: 34278303 Free PMC article.

16. PMID: 32430087
Frontal Behavior Syndromes in Idiopathic Normal Pressure Hydrocephalus as a Function of Alzheimer's Disease Biomarker Status.
Niermeyer M, Gaudet C, Malloy P, Piryatinsky I, Salloway S, Klinge P, Lee A. J Int Neuropsychol Soc. 2020 Oct;26(9):883-893. doi: 10.1017/S1355617720000387. Epub 2020 May 20.PMID: 32430087 Free PMC article.

17. PMID: 35852974
Not Just an Anchor: The Human Filum Terminale Contains Stretch Sensitive and Nociceptive Nerve Endings and Responds to Electrical Stimulation With Paraspinal Muscle Activation.
Klinge PM, McElroy A, Leary OP, Donahue JE, Mumford A, Brinker T, Gokaslan ZL.Neurosurgery. 2022 Oct 1;91(4):618-624. doi: 10.1227/neu.0000000000002081. Epub 2022 Jul 21.PMID: 35852974 Free PMC article.

18. PMID: 35307588
Diseased Filum Terminale as a Cause of Tethered Cord Syndrome in Ehlers-Danlos Syndrome: Histopathology, Biomechanics, Clinical Presentation, and Outcome of Filum Excision.
Klinge PM, Srivastava V, McElroy A, Leary OP, Ahmed Z, Donahue JE, Brinker T, De Vloo P, Gokaslan ZL.World Neurosurg. 2022 Jun;162:e492-e502. doi: 10.1016/j.wneu.2022.03.038. Epub 2022 Mar 17.PMID: 35307588 Free article.

19. PMID: 33298792
In Vivo Ultrasound Imaging of the Spinal Cord and Subarachnoid Space at the C1-C2 Level in Healthy Adult Subjects.
Beland MD, McElroy AW, Brinker T, Gokaslan ZL, Klinge PM. Ultrasound Q. 2020 Dec 9;38(1):49-52. doi: 10.1097/RUQ.0000000000000542.PMID: 33298792

20. PMID: 38866432
MRI-Based Prediction of Clinical Improvement after Ventricular Shunt Placement for Normal Pressure Hydrocephalus: Development and Evaluation of an Integrated Multisequence Machine Learning Algorithm.
Leary OP, Zhong Z, Bi L, Jiao Z, Dai YW, Ma K, Sayied S, Kargilis D, Imami M, Zhao LM, Feng X, Riccardello G, Collins S, Svokos K, Moghekar A, Yang L, Bai H, Klinge PM, Boxerman JL. AJNR Am J Neuroradiol. 2024 Oct 3;45(10):1536-1544. doi: 10.3174/ajnr.A8372.PMID: 38866432 Free PMC article.

21. PMID: 34247260
Imaging and health metrics in incidental cerebellar tonsillar ectopia: findings from the Adolescent Brain Cognitive Development Study (ABCD).
Nwotchouang BST, Ibrahimy A, Loth DM, Labuda E, Labuda N, Eppleheimer M, Labuda R, Bapuraj JR, Allen PA, Klinge P, Loth F. Neuroradiology. 2021 Nov;63(11):1913-1924. doi: 10.1007/s00234-021-02759-y. Epub 2021 Jul 11.PMID: 34247260

22. PMID: 39642381
Correlation of anterior CSF space in the cervical spine with Chicago Chiari Outcome Scale score in adult females.
Allen PA, Loth F, Loth D, Al Samman MM, Labuda R, Herrera C, Bapuraj JR, Klinge PM. J Neurosurg Spine. 2024 Dec 6;42(3):299-308. doi: 10.3171/2024.7.SPINE24370. Print 2025 Mar 1. PMID: 39642381

23. PMID: 40272153
Cognitive-Affective Improvement on Cerebellar Neuropsychiatric Rating Scale Scores in Adults and Children After Decompression of Chiari Malformation Type I.
Shao B, Leary OP, Sayied S, Wirth L, Amaral-Nieves N, Kozel OA, Svokos KA, Allen PA, Trask CL, Klinge PM. Neurosurgery. 2025 Apr 24. doi: 10.1227/neu.0000000000003481. Online ahead of print. PMID: 40272153

Contact Us

Computational Neuromodulation Laboratory 
593 Eddy Street 
Aldrich Building 
Providence RI 02903 
Phone: (401) 793-9177 | Fax: (401) 606-4011